Author:
Lv Yuan,Guo Xiangpeng,Hu Jieyi,Kanwal Shahzina,Yuan Jianwen,Tariq Muqddas,Zheng Jingxia,Sun Mingwei,Lu Yuanyuan,Wang Jingjing,Jiang Mengling,Wang Aiping,Castells-Garcia Alvaro,Zheng Xiyuan,Peng Bin,Wang Dongye,Volpe Giacomo,Wu Liang,Mazid Md. Abdul,Li Wenjuan,Lai Yiwei,Aguilo Francesca,Zhou Yu,Cosma Maria Pia,Xu Xingzhi,Lundberg Emma,Mulder Jan,Hutchins Andrew P.,Maxwell Patrick H.,Croce Luciano Di,Zhang Xiaofei,Esteban Miguel A.
Abstract
AbstractThe ability of RNA-binding proteins (RBPs) to form complexes with other biomolecules underpins a broad range of functions and remarkable structural properties. Understanding the precise spatiotemporal dynamics of RBPs and their interacting partners in the steady state and upon perturbation is key to deciphering these aspects. Here, we present the coRIC (compartmentalizedRNA InteractomeCapture) map, an experimental resource and analytical pipeline to study the subcellular dynamics of RBPs through multimodal dataset integration and machine learning. Using this approach, we have generated an atlas comprising 1,768 RBPs distributed in a broad panel of subcellular compartments and delineated their intermolecular and intercompartmental relationships. We have also defined the hierarchy of RBP-containing complexes at multiple scales across the cell, uncovering previously unknown functions of multiple RBPs. Furthermore, we have investigated the changes in RBP complex composition and subcellular distribution in response toC9ORF72amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRIC map provides a valuable new approach for defining the roles of RBPs in homeostasis and disease.
Publisher
Cold Spring Harbor Laboratory